NM_003672.4:c.50-45T>C

Variant names:

• chr1-100353717-T-C
• rs2297170
• NM_003672.4:c.50-45T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_003672.4(CDC14A):​c.50-45T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.184 in 1,009,098 control chromosomes in the GnomAD database, including 18,262 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.20 (3060 hom., cov: 32)
  • Exomes 𝑓: 0.18 (15202 hom.)
• Consequence: CDC14A NM_003672.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 0.796
• Publications: 7 publications found

Genes affected

CDC14A (HGNC:1718): (cell division cycle 14A) The protein encoded by this gene is a member of the dual specificity protein tyrosine phosphatase family. It is highly similar to Saccharomyces cerevisiae Cdc14, a protein tyrosine phosphatase involved in the exit of cell mitosis and initiation of DNA replication, suggesting a role in cell cycle control. This protein has been shown to interact with, and dephosphorylate tumor suppressor protein p53, and is thought to regulate the function of p53. Alternative splicing of this gene results in several transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

CDC14A Gene-Disease associations (from GenCC):

• nonsyndromic genetic hearing loss

  Inheritance: AR Classification: DEFINITIVE Submitted by: ClinGen
• autosomal recessive nonsyndromic deafness 105

  Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• hearing impairment and infertile male syndrome

  Inheritance: AR Classification: STRONG Submitted by: ClinGen
• hearing loss, autosomal recessive

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• autosomal recessive nonsyndromic hearing loss 32

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 1-100353717-T-C is Benign according to our data. Variant chr1-100353717-T-C is described in ClinVar as Benign. ClinVar VariationId is 682965.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.213 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_003672.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	NM_003672.4	MANE Select	c.50-45T>C		intron	N/A	NP_003663.2
	CDC14A	NM_033312.3		c.50-45T>C		intron	N/A	NP_201569.1	Q9UNH5-2
	CDC14A	NM_001319210.2		c.50-45T>C		intron	N/A	NP_001306139.1	Q9UNH5-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDC14A	ENST00000336454.5	TSL:1 MANE Select	c.50-45T>C		intron	N/A	ENSP00000336739.3	Q9UNH5-1
	CDC14A	ENST00000361544.11	TSL:1	c.50-45T>C		intron	N/A	ENSP00000354916.6	Q9UNH5-2
	CDC14A	ENST00000370124.8	TSL:1	c.50-45T>C		intron	N/A	ENSP00000359142.3	Q9UNH5-3

Frequencies

GnomAD3 genomes AF: 0.196 AC: 29852 AN: 152074 Hom.: 3050 Cov.: 32

Gnomad AFR AF: 0.217

Gnomad AMI AF: 0.191

Gnomad AMR AF: 0.165

Gnomad ASJ AF: 0.227

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.112

Gnomad FIN AF: 0.245

Gnomad MID AF: 0.158

Gnomad NFE AF: 0.194

Gnomad OTH AF: 0.189

GnomAD2 exomes AF: 0.174 AC: 31886 AN: 183530 AF XY: 0.173

Gnomad AFR exome AF: 0.218

Gnomad AMR exome AF: 0.110

Gnomad ASJ exome AF: 0.225

Gnomad EAS exome AF: 0.127

Gnomad FIN exome AF: 0.245

Gnomad NFE exome AF: 0.195

Gnomad OTH exome AF: 0.181

GnomAD4 exome AF: 0.182 AC: 156130 AN: 856906 Hom.: 15202 Cov.: 11 AF XY: 0.179 AC XY: 79933 AN XY: 445428

African (AFR) AF: 0.219 AC: 4703 AN: 21474

American (AMR) AF: 0.118 AC: 4192 AN: 35620

Ashkenazi Jewish (ASJ) AF: 0.221 AC: 4840 AN: 21856

East Asian (EAS) AF: 0.119 AC: 4292 AN: 36218

South Asian (SAS) AF: 0.106 AC: 7171 AN: 67594

European-Finnish (FIN) AF: 0.238 AC: 11832 AN: 49746

Middle Eastern (MID) AF: 0.194 AC: 602 AN: 3106

European-Non Finnish (NFE) AF: 0.191 AC: 110963 AN: 581322

Other (OTH) AF: 0.189 AC: 7535 AN: 39970

GnomAD4 genome AF: 0.196 AC: 29878 AN: 152192 Hom.: 3060 Cov.: 32 AF XY: 0.196 AC XY: 14595 AN XY: 74406

African (AFR) AF: 0.217 AC: 8989 AN: 41508

American (AMR) AF: 0.165 AC: 2520 AN: 15296

Ashkenazi Jewish (ASJ) AF: 0.227 AC: 788 AN: 3472

East Asian (EAS) AF: 0.126 AC: 652 AN: 5186

South Asian (SAS) AF: 0.111 AC: 538 AN: 4826

European-Finnish (FIN) AF: 0.245 AC: 2596 AN: 10582

Middle Eastern (MID) AF: 0.167 AC: 49 AN: 294

European-Non Finnish (NFE) AF: 0.194 AC: 13164 AN: 68006

Other (OTH) AF: 0.193 AC: 408 AN: 2112

Alfa AF: 0.192 Hom.: 3872

Bravo AF: 0.194

Asia WGS AF: 0.152 AC: 528 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	7.0
DANN	Benign	0.79
PhyloP100		0.80
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs2297170; hg19: chr1-100819273; COSMIC: COSV60560153;